This research seeks to study the cell-mediated immune response of mice to endogenous AKR leukemia viruses and syngeneic tumors induced by these viruses. H-2-restricted cytotoxic T-cell responses, T-cell proliferative responses and cellular responses resulting in the production of the nonspecific soluble mediator, interleukin-2 (IL-2), will be examined. The specificity of the H-2Kb- restricted cytotoxic T-cell response to Gross cell surface antigen-expressing tumor cells will be probed in a variety of ways including the use of an unsusceptible variant subclone (cl.18-5) of the susceptible AKR.H-2bSL1 tumor. The possibility that the target antigens recognized by such cytotoxic T cells may represent "preleukemic" antigens found on normal cells of leukemia-prone mice also will be addressed. The apparent requirement for stimulation with additional antigens other than the target antigens to induce these cellular immune responses will be examined to determine the nature of such required antigens and the cellular basis for their involvement. The genetics of responsiveness, including the effects of loci controlling virus production and/or viral antigen expression as well as loci linked to the H-2 complex, is also an area of intended research. Specifically, the possibility that genes mapping within H-2 and controlling cellular immune responses may exist and their relationship to known loci controlling resistance to leukemia will be tested.